In Pain? There's A Venom For That

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Black mamba snakes are among the deadliest serpents on Earth, but
their venom contains compounds that might help people overcome
pain.

For the first time, scientists have isolated compounds called
mambalgins from black mamba venom and injected them into mice.
The venom ingredients worked as well as morphine at dulling pain
in the rodents, but with fewer side effects and no toxic
consequences.

The compounds appear to work by blocking structures in the
nervous system called ion channels. People have these kinds of
structures, too.

"These channels become therefore new potential therapeutic
targets against pain," said Anne Baron, a molecular physiologist
at the Institute of Molecular and Cellular Pharmacology in
Valbonne, France. "It is remarkable that all of this was made
possible from the deadly venom of one of the most venomous
snakes."

Chronic pain affects some 20 percent of adults and half of all
elderly people, Baron said. But many of today's painkillers cause
side effects or lead to addiction, and many come with long-term
safety concerns.

In the search for better drugs, some researchers have turned to
the venoms of snakes, scorpions, spiders, cone snails and other
creatures. Over millions of years of evolution, these animals
have developed molecules with powerful effects on the nervous
systems and cardiovascular systems of their victims.

Baron and colleagues have been particularly interested in
structures called ASIC channels, which carry charged sodium atoms
or ions across the membranes of nerve cells and have been
implicated in causing pain in rodents, humans and other animals.

Previous research has shown that these ion channels appear in
several parts of the pain pathway, including in the neurons that
sense pain and in the spinal cord, where they send information to
the brain. When the channels are open, electrical signals pass
through.

Because some snake venoms are known to contain compounds that act
on ion channels, Baron's team decided to screen black mamba venom
for possibilities.

When the researchers discovered that the venom could block the
electric currents flowing through ASIC channels, they purified
the small protein compounds -- called peptides -- responsible for
the effect. These mambalgins made up less than half a percent of
the venom's proteins.

Finally, the team injected the mambalgins into mice before
subjecting the rodents to various kinds of pain, including the
immersion of a paw in water heated to 115 degrees Fahrenheit.
Armed with venom compounds, the mice were slower to withdraw
their paws from the water, the researchers report today in the journal
Nature. That means they felt less pain.

It will take years of further research to turn the finding into
new kinds of painkillers for people.

For now, the discovery helps illuminate some of the ways that
pain works and what role ion channels play in causing pain, said
David Julius, a neuroscientist at the University of California,
San Francisco. In his own work, he and colleagues have found that
pain-inducing toxic compounds in the Texas coral snake activate
the same channels that the black mamba compounds inhibit.

The new study also highlights the broad potential of venom to
inspire advances in medical research.

"Each of these venoms contain dozens if not hundreds of different
peptides or small molecules, and we've only likely tapped a small
component of that," Julius said. "There's a really great
pharmacopeia of things in there and a wealth of potential tools
and insights we can get from them. I'd say the potential is
huge."